med. Hubert Schrezenmeier is Head of the cell manufacturing centre in Ulm, which is co-localized at Ulm University and the Institute for Clinical Transfusion Medicine and Immunogenetics (IKT) at the Red Cross in Ulm, Germany. The centre has a manufacturing licence and MSCs are manufactured in a GMP-certified cleanroom. The GMP requirements ensure that the cell products are consistently produced and controlled in compliance with the established quality management system.
The Ex vivo facility staff visited the centre in Ulm during MSC manufacturing for a multicentre European clinical trial (Maxibone EU project) led and sponsored by Dr. Cecilie Gjerde and Prof. Kamal Mustafa at the Institute of Clinical Dentistry, University of Bergen (IKO-UiB). The manufacturing protocol has been approved by the Norwegian Medicines Agency, The Regional committees for medical and health research ethics (REK) and the National authorities in each participating country. A Voluntary Harmonisation Procedure (VHP) was used to get the approval.
In this protocol, cells are withdrawn from the bone marrow of patients participating in the clinical trial and shipped to the cell manufacturing centre in Ulm. During the manufacturing process, the MSCs are expanded to 100 million cell in 15 days. Furthermore, the cells undergo several steps of quality controls in compliance with the GMP requirements, before being shipped back to Bergen. As part of the clinical trial, the expanded MSCs will be transplanted back into the patient together with an advanced biomaterial that, in time, will trigger bone healing and generate new bone tissue.
Aim to obtain a GMP-certified facility for cell production in Bergen
Several projects affiliated with the Mohn Research Centre for Regenerative Medicine intend to use a similar MSC manufacturing protocol as described above in their clinical trials. At Haukeland University Hospital in Bergen, a cleanroom for cell manufacturing, the “Ex vivo facility
”, has recently been established. The personnel aim at obtaining GMP certification, manufacturing authorization and start the first cell production for use in clinical trials in 2023. The training in Ulm is part of the extensive training required for cleanroom employees, and the Ex vivo team are now one step closer to being certified for manufacturing cell products here in Bergen.
GMP: Good manufacturing practice (GMP) describes the minimum standard that a medicines manufacturer must meet in their production processes. The European Medicines Agency (EMA) coordinates inspections to verify compliance with these standards and plays a key role in harmonising GMP activities at European Union (EU) level.
: The MSCs are cell-based therapeutics intended for patient treatment in clinical trials and are classified as Advanced Therapy Medicinal Products (ATMP). Other ATMPs include gene therapy medicines and tissue-engineered medicines. Manufacturing of ATMPs intended for human use follows strict regulations and must be prepared in GMP-certified facilities that can ensure the product's microbiological safety.